RECRUITING

Senicapoc in Alzheimer's Disease

Conditions

Mild Cognitive Impairment Alzheimer Disease Amnestic Mild Cognitive Impairment (MCI)Mild AD dementia Senicapoc

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Development of novel disease-modifying therapies for Alzheimer's disease (AD) remains of paramount importance. This study will be a Phase II randomized clinical trial testing Senicapoc in patients with mild or prodromal AD. This will be a small Proof of Mechanism study to prove biological activity and target engagement in humans with early AD. The investigators will study up to 55 patients over 52 weeks, with primary outcomes being Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) scores and blood and cerebrospinal fluid (CSF) markers of neuroinflammation. This pilot study will provide an estimate of treatment effect size on cognitive trajectory, daily function, and brain atrophy.

Official Title

Proof of Mechanism Study of Senicapoc in Mild or Prodromal Alzheimer's Disease

Quick Facts

Study Start:2022-03-18

Study Completion:2026-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04804241

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:55 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age 55-85 * Fluent in either English or Spanish * Willing to be randomized to active drug (10 mg Senicapoc) vs. placebo (3:1 ratio) * Clinical Dementia Rating (CDR) global score of 1 or 0.5 * Education adjusted scores between 12-28 on the Montreal Cognitive Assessment (MoCA) at the Screening visit. * A consensus clinical diagnosis of either amnestic Mild Cognitive Impairment (MCI) or mild AD dementia. Diagnoses are made by a comprehensive case conference review for all participants in the ADRC longitudinal cohort and all CADC referrals, resulting in a consensus diagnosis made according to current research criteria. For patients referred from other clinics, the case will be reviewed by a study physician and neuropsychologist and only patients who satisfy criteria for probable AD (McKhann et al 1984) or amnestic MCI (Petersen et al 2004) will be eligible for enrollment. * Vision (with or without correction) of at least 20/50 for distant vision * All participants will need a study partner informant who has at least 6 hours of contact per week with the participant. The study partners are used to help answer questions on the subject's behalf, since many of them will be impaired and may need assistance with providing accurate information. The study partners are not asked to provide any opinions or judgements about the subjects. * For Females of childbearing potential: Must agree to practice a highly effective method of contraception throughout the study until completion of the Week 78 follow up visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of less than 1% per year when used correctly and consistently.	* Unstable medical illnesses including hepatic insufficiency (elevated ALT, AST, or GGT; or low albumin attributable to liver disease), renal insufficiency (CK-EPI stage 4 or higher, or estimated GFR \<30) * Unstable ischemic cardiovascular disease, respiratory failure, moderate or severe congestive heart failure - New York Heart Association class III or IV, cancer, unstable hematologic disease or a life expectancy of \<3 years * Use of experimental AD treatments * Unable to undergo MRI scanning (e.g. pacemaker, metallic implants, severe claustrophobia) * History of chronic psychiatric illness (e.g. schizophrenia), any episode of major depression within last 2 years, or current Geriatric Depression Scale (GDS) \> 6, any recent suicide attempts or suicidal ideation. Subjects with a diagnosis of bipolar disorder may be included if they have been clinically stable for a minimum of 3 years prior to the Screening visit. Clinical stability to be determined by the Principal Investigator. * History of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis), head trauma resulting in any persistent cognitive deficit * History of alcohol or drug abuse/dependence within the past 5 years * Known allergy to chemically related compounds (e.g. clotrimazole) * Lack of good venous access, such that multiple blood draws would be precluded * Regular use of any of these CNS active medications: benzodiazepines, antipsychotics, narcotics, or anti-epileptic drugs. Exceptions may be allowed by the Principal Investigator for regular use of low doses of CNS active medications. Subjects using any of these treatments will be instructed to hold their dose on the evening prior and the day of the efficacy visits (Baseline, Week 26 and Week 52). Stable doses (\> 6 weeks) of cholinesterase inhibitors or memantine will be allowed, as will stable doses of anti-depressants. * Female subjects who are pregnant or breastfeeding or who plan to become pregnant during participation in this trial * Inability to swallow oral tablets * Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter * History of bleeding diathesis or coagulopathy, * On anticoagulant therapy (within 14 days of lumbar puncture (LP), including but not limited to warfarin, heparin, dabigatran, rivaroxaban, and apixaban, * Requires daily antiplatelet therapy, including but not limited to aspirin (unless \< 81mg/day), clopidogrel, dipyridamole, and ticlopiidinegrel. However, the investigators will not exclude those who can safely hold antiplatelet therapy for 7 days prior to LP. Safety will be determined by the participant's Primary Care Provider and study PI. * For those who take antiplatelet therapy intermittently (e.g. aspirin as needed for pain), the investigators will exclude any doses within 48 hours of the LP or more than two dosses within 7 days of LP. * platelet count less than the lower limit of normal (platelet counts between 100,000 and 150,000 mm3 are permissible as long as the investigator confirms there is no evidence of current bleeding diathesis or coagulopathy) * The investigators will require INR/PT and aPTT labs to be done within 14 days of LP and will exclude those with INR \> 1.30 or abnormally elevated aPTT. * Does not have good venous access, such that multiple blood draws would be precluded * Prior radiation exposure of \> 2 rem total within last 12 months. * Probable AD dementia patients with a global cortical SUVr \< 1.08.

Inclusion Criteria

Exclusion Criteria

* Age 55-85
* Fluent in either English or Spanish
* Willing to be randomized to active drug (10 mg Senicapoc) vs. placebo (3:1 ratio)
* Clinical Dementia Rating (CDR) global score of 1 or 0.5
* Education adjusted scores between 12-28 on the Montreal Cognitive Assessment (MoCA) at the Screening visit.
* A consensus clinical diagnosis of either amnestic Mild Cognitive Impairment (MCI) or mild AD dementia. Diagnoses are made by a comprehensive case conference review for all participants in the ADRC longitudinal cohort and all CADC referrals, resulting in a consensus diagnosis made according to current research criteria. For patients referred from other clinics, the case will be reviewed by a study physician and neuropsychologist and only patients who satisfy criteria for probable AD (McKhann et al 1984) or amnestic MCI (Petersen et al 2004) will be eligible for enrollment.
* Vision (with or without correction) of at least 20/50 for distant vision
* All participants will need a study partner informant who has at least 6 hours of contact per week with the participant. The study partners are used to help answer questions on the subject's behalf, since many of them will be impaired and may need assistance with providing accurate information. The study partners are not asked to provide any opinions or judgements about the subjects.
* For Females of childbearing potential: Must agree to practice a highly effective method of contraception throughout the study until completion of the Week 78 follow up visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of less than 1% per year when used correctly and consistently.

* Unstable medical illnesses including hepatic insufficiency (elevated ALT, AST, or GGT; or low albumin attributable to liver disease), renal insufficiency (CK-EPI stage 4 or higher, or estimated GFR \<30)
* Unstable ischemic cardiovascular disease, respiratory failure, moderate or severe congestive heart failure - New York Heart Association class III or IV, cancer, unstable hematologic disease or a life expectancy of \<3 years
* Use of experimental AD treatments
* Unable to undergo MRI scanning (e.g. pacemaker, metallic implants, severe claustrophobia)
* History of chronic psychiatric illness (e.g. schizophrenia), any episode of major depression within last 2 years, or current Geriatric Depression Scale (GDS) \> 6, any recent suicide attempts or suicidal ideation. Subjects with a diagnosis of bipolar disorder may be included if they have been clinically stable for a minimum of 3 years prior to the Screening visit. Clinical stability to be determined by the Principal Investigator.
* History of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis), head trauma resulting in any persistent cognitive deficit
* History of alcohol or drug abuse/dependence within the past 5 years
* Known allergy to chemically related compounds (e.g. clotrimazole)
* Lack of good venous access, such that multiple blood draws would be precluded
* Regular use of any of these CNS active medications: benzodiazepines, antipsychotics, narcotics, or anti-epileptic drugs. Exceptions may be allowed by the Principal Investigator for regular use of low doses of CNS active medications. Subjects using any of these treatments will be instructed to hold their dose on the evening prior and the day of the efficacy visits (Baseline, Week 26 and Week 52). Stable doses (\> 6 weeks) of cholinesterase inhibitors or memantine will be allowed, as will stable doses of anti-depressants.
* Female subjects who are pregnant or breastfeeding or who plan to become pregnant during participation in this trial
* Inability to swallow oral tablets
* Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
* History of bleeding diathesis or coagulopathy,
* On anticoagulant therapy (within 14 days of lumbar puncture (LP), including but not limited to warfarin, heparin, dabigatran, rivaroxaban, and apixaban,
* Requires daily antiplatelet therapy, including but not limited to aspirin (unless \< 81mg/day), clopidogrel, dipyridamole, and ticlopiidinegrel. However, the investigators will not exclude those who can safely hold antiplatelet therapy for 7 days prior to LP. Safety will be determined by the participant's Primary Care Provider and study PI.
* For those who take antiplatelet therapy intermittently (e.g. aspirin as needed for pain), the investigators will exclude any doses within 48 hours of the LP or more than two dosses within 7 days of LP.
* platelet count less than the lower limit of normal (platelet counts between 100,000 and 150,000 mm3 are permissible as long as the investigator confirms there is no evidence of current bleeding diathesis or coagulopathy)
* The investigators will require INR/PT and aPTT labs to be done within 14 days of LP and will exclude those with INR \> 1.30 or abnormally elevated aPTT.
* Does not have good venous access, such that multiple blood draws would be precluded
* Prior radiation exposure of \> 2 rem total within last 12 months.
* Probable AD dementia patients with a global cortical SUVr \< 1.08.

Contacts and Locations

Study Contact

Rita Venua

CONTACT

(916) 734-1708

rmvenua@ucdavis.edu

Hongzheng Zhang

CONTACT

(925) 357-6914

hzzhang@ucdavis.edu

Principal Investigator

John Olichney, MD

PRINCIPAL_INVESTIGATOR

University of California, Davis

Study Locations (Sites)

University of California, Davis Alzheimer's Disease Center

Sacramento, California, 95817

United States

UC Davis Alzheimer's Disease Center East Bay

Walnut Creek, California, 94598

United States

Collaborators and Investigators

Sponsor: University of California, Davis

John Olichney, MD, PRINCIPAL_INVESTIGATOR, University of California, Davis

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-18

Study Completion Date2026-06

Study Record Updates

Study Start Date2022-03-18

Study Completion Date2026-06

Terms related to this study

Keywords Provided by Researchers

Amnestic Mild Cognitive Impairment (MCI)
Mild AD dementia
Senicapoc

Additional Relevant MeSH Terms

Mild Cognitive Impairment
Alzheimer Disease